1. Field of the Invention
The invention relates to a new chemical process for preparing certain known chemical compounds, valuable in the art by virtue of their ability to lower blood pressure in hypertensive mammals. More specifically, these hypotensive agents are certain 2-(4-aroylpiperazin-1-yl)-4-amino-6,7-dimethoxyquinazolines, use of which is taught in U.S. Pat. No. 3,511,836. The invention also relates to certain novel 2-(4-substituted-piperazin-1-yl)-4-amino-6,7-dimethoxyquinazolines wherein said substituent is cyano, or one of certain N,N-disubstituted carbamyl, imido ester, imido thiolester or amidino groups, which are useful as intermediates in the process of the invention.
2. Description of the Prior Art
U.S. Pat. No. 3,511,836 discloses several processes for the preparation of 2-(4-substituted piperazin-1-yl)-4-amino-6,7-dimethoxyquinazolines. For example, by the reaction of 2-chloro-4-amino-6,7-dimethoxyquinazoline with the appropriate 1-substituted piperazine, by reaction of a 2-(4-substituted piperazin-1-yl)-4-chloro-6,7-dimethoxyquinazoline with ammonia or by alkylation, alkanoylation, aroylation or alkoxylation of 2-(2-piperazinyl)-4-amino-6,7-dimethoxyquinazoline. U.S. Pat. No. 3,669,968 teaches the preparation of 2-(4-substituted piperazin-1-yl)-4-amino-6,7,8-trimethoxyquinazolines via reaction of 2-chloro-4-amino-6,7,8-trimethoxyquinazoline with the appropriate 1-substituted piperazine.
In U.S. Pat. No. 3,935,213 processes are disclosed whereby 2-(4-substituted-piperazin-1-yl)-4-amino-6,7-dimethoxyquinazolines and the corresponding 6,7,8-trimethoxyquinazolines are produced by either: (1) reaction of the appropriate 4,5-dimethoxy-substituted or 3,4,5-trimethoxy-substituted 2-aminobenzonitrile with certain 1,4-disubstituted piperazines; or (2) reaction of the appropriate 4,5-dimethoxy- or 3,4,5-trimethoxy-substituted 2-aminobenzamidine with the same 1,4-disubstituted piperazines.
2-(4-Alkoxycarbonylpiperazin-1-yl)-4-amino-6,7-dimethoxyquinazolines which are useful intermediates in the process of the invention are disclosed and claimed in U.S. Pat. No. 3,511,836. However, other intermediates which are useful in the instant process are novel compounds.